1-hydroxy-6-substituted pyridine-2-ones and 1-hydroxy-6-substituted pyridine-2-thiones for biocidal use

ABSTRACT

The present invention relates to novel 1-hydroxy-6-substituted pyridine-2-one and 1-hydroxy-6-substituted pyridine-2-thione compounds. Also disclosed is a process for producing the compound(s) and an antimicrobial composition comprising the compound(s) and at least one component selected from the group consisting of soaps, adhesives, coatings, elastomers, sealants, shampoos, skin care medicaments, cosmetics, paints and other polymer compositions.

This application is a continuation-in-part application of U.S. Ser. No.08/137,521 filed Oct. 18, 1993, now U.S. Pat. No. 5,424,435.

FIELD OF THE INVENTION

This invention relates to novel 1-hydroxy-6-substituted pyridine-2-onesand 2-thiones, a process for their preparation, and their use asbiocides. These compounds exhibit good biocidal activity, particularlyantifungal activity.

BACKGROUND OF THE INVENTION

Compounds exhibiting biocidal activity are well known in the art. Forexample, pyrithione salts, such as zinc pyrithione, are known to provideexcellent biocidal activity, including broad spectrum anti-bacterial andanti-fungal activity. There are many uses for these pyrithiones. By wayof illustration, U.S. Pat. No. 4,818,436 discloses the use ofpyrithiones in metalworking fluids, U.S. Pat. No. 4,401,770 disclosesurethane shoe inserts having antimicrobial activity; and U.S. Pat. No.4,935,061 discloses their use in paints.

Despite the excellent biocidal (particularly fungicidal) activityattributable to pyrithione salts, these compounds do have drawbacks forcertain applications, most notably limited solubility in certain organicsolvents and aqueous media. Accordingly, new compounds exhibitingexcellent biocidal activity, but also exhibiting good solubility inorganic solvents would be useful to the biocides manufacturingcommunity.

One compound that exhibits good biocidal efficacy and solubility inshampoo formulations is1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone. Unfortunately,this compound is more expensive to manufacture than otherwise might bedesired. This compound and related compounds are disclosed in U.S. Pat.No. 3,883,545; their use in combating dandruff is described in U.S. Pat.No. 4,185,106; and their use in an antidandruff shampoo is described inU.S. Pat. No. 4,711,775. U.S. Pat. No. 4,916,228 discloses thepreparation of a broad class of 1-hydroxy-2-pyridones by a processcomprising reacting a pyrone having a specified structural formula witha hydroxylammonium salt in the presence of at least one alkali metalcarbonate and/or hydrogen carbonate.

A technical journal publication entitled "QuantitativeStructure-Activity Analysis in a Series of Antimycotically ActiveN-Hydroxypyridones", Journal of Medicinal Chemistry, 1974, Vol. 17, No.7, p. 753, describes a variety of 1-hydroxy-substituted-2-pyridones,including those having para-substitutions of --SCH₂ C₆ H₄ Cl (compound15 in Table II thereof) and --OCH₂ C₆ H₄ Cl (compound 16 in Table IIthereof), as having antimycotic activity. However, the method ofpreparation of these compounds is not described in this technicalpublication, and it is believed that these compounds were made from6-chloro-2-pyrone which is not commercially available.

Other new biocides providing desired solubility characteristics, as wellas new processes for their preparation, would be highly desired by thebiocides manufacturing community.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a compound of theformula: ##STR1## wherein X is an oxygen or sulfur moiety and R is asubstituted or unsubstituted hydrocarbon radical having between 1 and 20carbon atoms, with the proviso that R is other than chlorobenzyl.

In another aspect, the present invention relates to a compound of theformula: ##STR2## wherein Y is an oxygen, sulfur, or NR' moiety whereinN is nitrogen and R and R' are independently each a substituted orunsubstituted hydrocarbon radical having between 1 and 20 carbon atoms.

In yet another aspect, the present invention relates to a compound ofthe formula: ##STR3## wherein R" and R'" are independently eitherhydrogen or a substituted or unsubstituted hydrocarbon radical havingbetween 1 and 20 carbon atoms, with the proviso that either R or R' is ahydrocarbon radical.

Preferred hydrocarbon radicals for the R group in the above formulae(I), (II), and (III) are aliphatic hydrocarbons having between 3 and 15carbons, more preferably a straight chain hydrocarbon having between 5and 10 carbons. The term "substituted hydrocarbon" is intended toinclude substituents such as halogen such as chloro, iodo fluoro orbromo, alkoxy such as methoxy, ethoxy, propoxy or butoxy, nitro, thio,amino combinations thereof, and the like. Illustrative hydrocarbongroups include n-octyl, 2,4,4-trimethylpentyl, 3,5,5-trimethylhexyl,combinations thereof, and the like.

In still another aspect, the present invention relates to a process forproducing compound of Formulae (I) or (II) wherein X or Y is oxygenwhich comprises the steps of:

(a) reacting 2,6-dichloropyridine N-oxide, a hydroxy compound containingbetween 1 and 20 carbon atoms (such as an alcohol such as n-octanol or aphenol compound such as 4-methylphenol, preferably selected from thegroup consisting of alkyl, arylalkyl and aryl compounds containing atleast one hydroxyl group, and combinations thereof) and a base (such assodium hydroxide or potassium hydroxide), optionally in the presence ofwater or an organic solvent, at an elevated temperature to produce acorresponding 2-chloro-6-substituted-pyridine N-oxide and

(b) reacting said 2-chloro-6-substituted-pyridine N-oxide with a base toproduce the corresponding 1-hydroxy-6-substituted-pyridine-2-one.

In yet another aspect, the present invention relates to a process forproducing a compound of Formula (II) wherein Y is nitrogen or a compoundof Formula (III) which comprises the steps of:

(a) reacting 2,6-dichloropyridine N-oxide, a primary or secondary aminecontaining between 1 and 20 carbon atoms (such as dimethanolamine ortriethanolamine) and a base (such as sodium hydroxide or potassiumhydroxide), optionally in the presence of water or an organic solvent,at an elevated temperature to produce a corresponding2-chloro-6-substituted-pyridine N-oxide and

(b) reacting said 2-chloro-6-substituted-pyridine N-oxide with asulfur-containing base to produce the corresponding1-hydroxy-6-substituted-pyridine-2-thione.

In still another aspect, this invention relates to a process forproducing the compound of Formula (I) or (II), wherein X or Y is sulfur,which comprises the following steps:

(a) reacting a 2,6-dichloro pyridine N-oxide, a thiol compound havingbetween 1 and 20 carbon atoms, (for example alkyl, arylalkyl and arylthiol compounds, and combinations thereof) and base (such as sodiumhydroxide or potassium hydroxide) in an organic solvent at an elevatedtemperature to produce a corresponding 2-chloro-6-substituted-pyridineN-oxide and

(b) reacting said 2-chloro-6-substituted-pyridine N-oxide with a base toproduce the corresponding 1-hydroxy-6-substituted pyridine-2-one (i.e.,the compound of formula (I)) or 1-hydroxy-6-substitutedpyridine-2-thione (i.e., the compound of formula (II)).

The above processes can be carried out sequentially or simultaneously ina single step. Surfactants and/or phase transfer catalysts areoptionally employed to facilitate the step (a) reaction in any of theseprocesses.

In yet another aspect, the present invention relates to an antimicrobialcomposition comprising a functional component selected from the groupconsisting of paints, adhesives, coatings, elastomers, sealants,shampoos, skin care medicaments and metalworking fluid plus anantimicrobially effective amount of a compound represented by the aboveFormula (I) (II), or (III), or a salt of the compound of Formula (I)(II), or (III). Illustrative salts include the amine salts, alkali metaland alkaline earth metal salts and the like.

In still another aspect, the invention relates to a method forinhibiting the growth of microorganisms by contacting saidmicroorganisms with a composition containing an antimicrobial effectiveamount of a one of the above-described 1-hydroxy-6-substitutedpyridine-2-ones, 1-hydroxy-6-substituted pyridine-2-thiones, a saltthereof, or a combination thereof, of this invention and at least onecomponent selected from the group consisting of soaps, shampoos, skincare medicaments, cosmetics, and other polymer compounds such asadhesives, coatings, elastomers, sealants and paints.

These and other aspects will become apparent upon reading the followingdetailed description of the invention.

DETAILED DESCRIPTION OF THE INVENTION

It has now been surprisingly discovered that a straightforward processcan be employed to produce 1-hydroxy-6-substituted-2-pyridones or1-hydroxy-6-substituted-2-thiones, utilizing readily available startingmaterials. These compounds provide excellent antimicrobial efficacy andare inexpensive to produce.

The novel 1-hydroxy-6-substituted pyridine-2-one and1-hydroxy-6-substituted pyridine-2-thione compounds of this inventionare shown formulae (I), (II) and (III) given above.

The reactions of the processes of this invention are suitably conductedat atmospheric pressure, although higher or lower pressures may be usedif desired. Suitable reaction temperatures for steps (a) and (b) rangebetween a temperature of about 25° C. to about 150° C., preferablyemploying a reflux temperature of between about 70° C. and about 90° C.Total reaction time for the process of this invention can vary over awide range, but is advantageously between 30 minutes and 5 hours forstep (a) and between thirty minutes and 5 hours for step (b).

The reactions of the processes of this invention are suitably carriedout in the presence of a base and an organic solvent. Suitable basesinclude alkali metal hydroxides such as sodium hydroxide or potassiumhydroxide, alkaline earth metal hydroxides such as calcium or magnesiumhydroxide, pyridine, triethylamine and other tertiary amine bases,potassium carbonate, "DABCO" amine catalyst(1,4-diazabicyclo(2.2.2)octane), "DBU"(1,8-diazabicyclo(5.4.0)undec-7-ene), "DBN"(1,5-diazabicyclo(4.3.0)non-5-ene, t-butyltetramethyl-guanidine,combinations thereof, and the like. Preferred bases for step (a) areanhydrous, granular or powdered sodium or potassium hydroxide, andpreferred bases for step (b) are concentrated aqueous solutions ofsodium or potassium hydroxide having a concentration of base of betweenabout 10% and about 90% by weight based upon the weight of the solution.Preferably, the base is employed in at least an amount equal to thenumber of moles for each reactant, and a molar excess of base relativeto each reactant can be employed as desired.

The reactions of the processes of this invention are suitably carriedout in the presence of a solvent. Suitable organic solvents include, forexample, ether, and acetone, methylene chloride, benzene, toluene,pyridine, tetrahydrofuran ("THF"), acetonitrile, dimethylsulfoxide("OMSO"), dimethylformamide ("DMF"), and combinations thereof. Althoughthe preferred solvent is acetonitrile, it is more preferred to run thereactions neat. As another alternative, a reactive solvent can beemployed, if desired, for example by using an organic alcohol, e.g.isopropanol, or n-octanol, in an amount sufficient to provide thedesired reactant and solvent characteristics.

The molar ratio of reactants for the processes of this invention canvary over a wide range, but is preferably between 10:1 and 1:10, morepreferably between 2:1 and 1:2, most preferably about 1:1.

The antimicrobial compositions of this invention suitably comprise anantimicrobially effective amount of a compound as defined by thestructural formulae given herein above, and combinations thereof, and atleast one component selected from the group consisting of soaps,shampoos, skin care medicaments, cosmetics and paints. The antimicrobialcompound can be employed as is or in the form of a salt, such as anamine salt, such as the monoethanolamine ("MEA") salt, and the use ofthe salt form is preferred. By the term "antimicrobial effective amount"is meant an amount sufficient to impart to the compositions resistanceagainst microbial attack by fungi and/or bacteria. Preferably theantimicrobial compounds are employed in the composition in a totalamount of between about 0.01 and about 10 weight percent, morepreferably between about 0.01 and about 5 weight percent, based upon thetotal weight of the composition. A particularly preferred use for thebiocidal compounds of the present invention is in personal care productssuch as in shampoos and other hair care products, as well as in paint,paint bases and polymer compositions such as adhesive coatings,sealants, elastomers, acids and the like.

With respect to paints improved organic solubility and biocidal efficacyassociated with the compounds of the present invention are expected toprovide advantages when used in a wide variety of paints, includingindoor and outdoor household paints, industrial and commercial paintsand in particular marine paints for use, for example, or ships hulls.

Typically, a paint composition will contain a resin, a pigment andvarious optional additives such as thickening agent(s), wetting agentsand the like, as is well known in the art. The resin is preferablyselected from the group consisting of vinyl, alkyl, epoxy, acrylic,polyurethane and polyester resins, and combinations thereof. The resinis preferably employed in an amount of between about 20% and about 80%based upon the weight of the paint or paint base.

In addition, the paint composition of the present invention containsoptional additional additives which have a favorable influence on theviscosity, the wetting power and the dispersibility, as well as on thestability to freezing and electrolytes and on the foaming properties. Ifa marine paint is being fabricated, the paint preferably contains aco-biocide such as cuprous oxide or copper thio-cyanate, a swellingagent to cause the paint to gradually "slough off" in its marineenvironment, thereby causing renewed biocidal efficacy of newly exposedbiocide at the surface of the paint in contact with the water medium ofthe marine environment. Illustrative swelling agents arenaturally-occurring or synthetic clays, such as kaolin, montomorillonite(bentonits, clay mica (muscovite), and chlorite (hectonite), and thelike. In addition to clays, other swelling agents, including natural orsynthetic polymers, such as that commercially available as POLYMERGEL,have been found to be useful in the compositions of the presentinvention to provide the desired "sloughing off" effect. Swelling agentscan be used singly or in combination. The total amount of optionaladditives is preferably no greater than 20% by weight, more preferablybetween about 1% and about 5% by weight, based upon the total weight ofthe paint composition.

Illustrative thickening agents include cellulose derivatives, forexample methyl, hydroxyethyl, hydroxypropyl and carboxymethyl cellulose,poly(vinyl alcohol), poly (vinylpyrolidone), poly(ethylene-glycol),salts of poly(acrylic acid) and salts of acrylic acid/acrylamidecopolymers.

Suitable wetting and dispersing agents include sodium polyphosphate,salts of low-molecular-weight poly(acrylic acid), salts ofpoly(ethane-sulfonic acid), salts of poly (vinyl-phosphonic acid), saltsof poly(maleic acid) and salts of copolymers of maleic acid withethylene, 1-olefins with 3 to 18 carbon atoms and/or styrene.

In order to increase the stability to freezing and electrolytes theremay be added to the paint composition various monomer 1,2-diols, forexample glycol, propylene-glycol-(1,2), and butylene-glycol-(1,2) orpolymers thereof, or ethoxylated compounds, for example reactionproducts of ethylene oxide with long-chain alkanols, amines, carboxylicacids, carboxylic acid amides, alkyd phenols, poly(propylene-glycol) orpoly(butylene-glycol). The minimum temperature of film formation (whitepoint) of the paint composition may be reduced by adding solvents, suchas ethylene-glycol, butyl-glycol, ethyl-glycol acetate, ethyl-diglycolacetate, butyl-diglycol acetate, benzene or alkylated aromatichydrocarbons. As defoaming agents there are suitable for examplepoly(propylene-glycol) and polysiloxanes.

The compounds of the present invention have many desirable attributes.They possess good antimicrobial activity and are compatible withcomponents of conventional soaps, shampoos, skincare medicaments,plastics and other polymer compositions and the like. These polymers arealso non-volatile, hydrolytically-stable, thermally-stable and may besoluble in water and organic solvents. Furthermore, they form noundesirable colors in typical personal care items. Still further, theyare expected to be favorably cost competitive with known antimicrobialadditives used in conventional skin care formulations.

The following examples are intended to illustrate, but in no way limitthe scope of, the present invention. In the examples, the term "g"denotes grams, "mol" denotes moles, and all percents are given on aweight basis unless otherwise specified.

EXAMPLES Example 1 Preparation of1-Hydroxy-6-isopropyloxypyridine-2(1H)-ones

The 0.82 g (0.0050 moles) of 2,6-dichlopyridine N-oxide and 0.78 g(0.013 moles) of isopropanol was reacted with 0.210 g (0.0050 moles) ofground sodium hydroxide in 8.2 ml of DMSO at 80° C. overnight to give2-chloro-6-isopropyloxypyridine N-oxide. The excess of isopropanol wasremoved in vacuo and 0.800 g (0.020 mole) of ground sodium hydroxide wasreacted at 3 hours at 100° C. to give1-hydroxy-6-isopropyloxypyridine-2(1H)-one. After cooling, it was added74 ml of water and was adjusted with 6N HCl to pH 5. It was extractedwith ethyl acetate (3×25 ml). The ethyl acetate extract was washed withwater (2×10 ml) and dried over sodium sulfate. The solution wassaturated with sodium chloride and was extracted with ethyl acetate(3×25 ml). The ethyl acetate extract was washed with water (2×10 ml) anddried over sodium sulfate. The combined ethyl acetate extracts werefiltered and stripped in vacuo to give 0.50 g (59%). It wasrecrystallized from 5 ml of ethyl acetate, 5 ml of hexanes, andactivated carbon: mp 119°-120° C.

Example 2 Preparation of1-Hydroxy-6-(2,4,4-trimethylpentyloxy)pyridine-2(1H)-one

The 0.82 g (0.0050 moles) of 2,6-dichloropyridine N-oxide and 0.664 g(98%) (0.0050 moles) of 2,4,4-trimethyl-1-pentanol was reacted with0.211 g (0.0050 moles) of ground sodium hydroxide in 8.2 ml of DMSO at100° C. overnight to give 2-chloro-6-(2,4,4-trimethypentyloxy)pyridineN-oxide. It was reacted with 0.600 g (0.015 moles) of ground sodiumhydroxide at 100° C. for 4.5 hours to give1-hydroxy-6-(2,4,4-trimethylpentyloxy)pyridine-2(1H)-one. After cooling,it was added 74 ml of water and was adjusted with 6N HCl to pH 3. It wasextracted with ethyl acetate (3×25 ml). The combined ethyl acetateextract was washed with a saturated sodium chloride solution (2×10 ml)and dried over sodium sulfate. The ethyl acetate extract was filteredand stripped in vacuo to give 1.08 g (90%). It was recrystallized fromethyl acetate and hexanes: mp 133.5°-134° C.

Example 3 Preparation of1-Hydroxy-6-(3,5,5-trimethylhexyloxy)pyridine-2(1H)-one

The 0.82 g (0.0050 moles) of 2,6-dichloropyridine N-oxide and 0.80 g(90%) (0.0050 moles) of 3,5,5-trimethyl-1-hexanol was reacted with 0.206g (0.0050 moles) of ground sodium hydroxide in 8.2 ml of DMSO at 80° C.for 8.5 hours to give 2-chloro-6-(3,5,5-trimethylhexyloxy)pyridineN-oxide. It was reacted with 0.600 g (0.015 moles) of ground sodiumhydroxide at 80° C. for 4 hours to give1-hydroxy-6-(3,5,5-trimethy-hexyloxy) pyridine-2(1H)-one. After cooling,it was added 74 ml of water and was adjusted with 6N HCL to pH 3. Theprecipitate was filtered and washed with water to give 0.577 g (45%). Itwas recrystallized from ethyl acetate and hexanes: mp 130.5°-131° C.

Example 4 Preparation of 1-Hydroxy-6-octyloxypyridine-2(1H)-one

The 0.82 g (0.0050 moles) of 2,6-dichloropyridine N-oxide and 0.658 g(99%) (0.0050 moles) of 1-octanol was reacted with 0.200 g (0.0050moles) of ground sodium hydroxide in 8.2 ml of DMSO at 80° C. for 4.5hours to give 2-chloro-6-octyloxypyridine N-oxide. It was reacted with0.600 g (0.015 moles) of ground sodium hydroxide at 80° C. for 2.5 hoursto give 1-hydroxy-6-octyoxypyridine-2(1H)-one. After cooling, it wasadded 74 ml of water and was adjusted with 6N HCL to pH 3. Theprecipitate was filtered and washed with water to give 0.577 g (48%). Itwas recrystallized from ethanol and hexanes: mp 119°-120° C.

Example 5 Preparation of 1-Hydroxy-6-octylthiopyridine-2(1H)-one

The 2.01 g (0.0122 moles) of 2,6-dichloropyridine N-oxide and 2.10 g(85%) (0.0122 moles) of 1-octylmercaptan was reacted with 0.488 g(0.0122 moles) of ground sodium hydroxide in 8.2 ml of DMSO at 80° C.for 6 hours to give 2-chloro-6-octylthiopyridine N-oxide. It was reactedwith 1.47 g (0.0367 moles) of ground sodium, hydroxide at 80° C. for 3hours to give 1-hydroxy-6-octylthiopyridine-2(1H)-one. After cooling, itwas added 180 ml of water and was adjusted with 6N HCL to pH 3. Theprecipitate was filtered, washed with water and washed with 150 ml ofpetroleum ether to give 1.34 g (43%).

Example 6 Preparation of 1-Hydroxy-6-octylsulfonylpyridine-2(1H)-one

The 0.204 g (0.00080 moles) of 1-hydroxy-6-octylthiopyridine-2(1H)-onewas reacted with 0.36 ml (0.0032 moles) of 30% hydrogen peroxide in 2.0ml of glacial acetic acid for overnight at room temperature to give1-hydroxy-6-octylsulfonyl pyridine-2(1H)-one. It was stripped in vacuoand was then dissolved with ethanol and stripped in vacuo three times togive 0.22 g. It was recrystallized from acetone and petroleum ether.

Example 7 Preparation of 1-Hydroxy-6-thiophenylpyridine-2(1H)-one

The 1.64 g (0.010 moles) of 2,6-dichloropyridine N-oxide and 1.11 g(99%) (0.010 moles) of thiophenol was reacted with 0.400 g (0.010 moles)of ground sodium hydroxide of 16.4 ml of DMSO at 80° C. for 5 hours togive 2-chloro-6-thiophenylpyridine N-oxide. It was reacted with 1.20 g(0.030 moles) of ground sodium hydroxide at 80° C. for 2.5 hours to give1-hydroxy-6-thiophenylpyridine-2(1H)-one. After cooling, it was added148 ml of water and was adjusted with 6N HCl to pH 3. The precipitatewas filtered, washed with water and washed with hexanes to give 1.64 g(75%). It was recrystallized from ethanol: mp 180°-181° C.

Example 8 Preparation of 1-Hydroxy-6-thiophenylsulfonypyridine-2(1H)-one

The 1.00 g (0.00456 moles) of 1-hydroxy-6-thiophenylpyridine-2(1H)-onereacted with 1.30 ml (0.0114 moles) of 30% hydrogen peroxide in 5 ml ofglacial acetic acid at room temperature overnight. The precipitate wasdissolved with more 5 ml of glacial acetic acid and was then added 1.30ml (0.0114 moles) of 30% hydrogen peroxide at room temperature over theweekend. The precipitate was filtered and washed with hexanes to give0.624 g. The acetic acid and the hexanes were stripped in vacuo to give0.45 g. The combined product gave 1.14 g (93%).

Example 9 Preparation of 1-Hydroxy-6-phenyloxypyridine-2(1H)-one

The 0.82 g (0.0050 moles) of 2,6-dichloropyridine N-oxide and 0.47 g(0.0050 moles of phenol was reacted with 0.200 g (0.0050 moles) ofground sodium hydroxide in 8.2 ml of DMSO at 80° C. for 6 hours to give2-chloro-6-phenyloxypyridine N-oxide. It was reacted with 0.600 g (0.015moles) of ground sodium hydroxide at 80° C. for 3.5 hours to give1-hydroxy-6-phenyoxypyridine-2(1H)-one. After cooling, it was added 74ml of water and was adjusted with 6N HCl to pH 3. The water solution wasextracted with dichloromethane (2×25 ml) and was dried over sodiumsulfate. The dichloromethane solution was stripped in vacuo to give 1.29g which was purified with Flash Chromatography(9:1 ethylacetate:methanol):0.82 (65%).

Example 10 Preparation of 1-hydroxy-6-octylaminopyridine-2(1H)-ones

To 1.53 g(0.008moles) of 2,6-dichloropyridine in 13.3 ml of toluene wasadded 1.26 g) 0.0162 moles) 1-octylamine and refluxed for 3 hours. Thereaction content was cooled to room-temperature, washed several timeswith water to yield 2.02 g of 2-chloro-6-octylaminopyridine-N-oxide as ayellow liquid.

The yellow liquid refluxed with 2.7 g of potassium tert-butoxide intert-butyl alcohol overnight. Water was added to the reaction flask anda precipitate was formed upon adjustment of pH to 3. The precipitatefiltered and washed to yield 1.36 g of product.

Example 11 Preparation of 1-hydroxy-6-octyloxpyridine-2(1H)-thiones

2-Chloro-6-octyloxypyridine-N-oxide was prepared according to Example 4and subsequent reaction with NaSH in acetonitle and extraction withmethylene chloride yielded the product as white powder.

Example 12 Preparation of 1-hydroxy-6-octylaminoyridine-2(1H)-thiones

A reaction mixture of 0.52 g of 2-chloro-6-octylaminopyridine-N-oxide(prepared as described in Example 10), 5 ml DMSO and 0.55 ml of 46%solution of NaSH was heated at 80 degrees for two hours. The reactionwas diluted with water, pH was adjusted to three, and the product wasextracted with methylene chloride.

Example 13 Proposed example for preparation of1-hydroxy-6-octylthiopyridine-2(1H)-thiones

2-Chloro-6-octylthiopyridine-N-oxide is prepared according to the methoddescribed in Example 5, and subsequent reaction with aqueous solution ofNaSH yields the titled product.

Determination of the Minimum Inhibitory Concentrations (MIC's) forAntimicrobial Compounds of this Invention

Solutions of the experimental compounds in dimethyl sulfoxide wereserially diluted in nutrient broth (Tryptic Soy Broth for bacteria andSabouraud Dextrose Broth for fungi) in microliter plates. Equal volumesof a broth suspension of bacteria (10⁶ CFU/ml) or fungi (10⁵ cells orspores/ml) were added to each dilution, and the plates were incubated at37° C. (bacteria and yeast) or 28° C. (molds). Bacteria, yeast and moldswere incubated two, five and seven days respectively before determiningthe highest inhibitory dilution.

                  TABLE I                                                         ______________________________________                                        MIC (ppm)                                                                     MIC of the 1-hydroxy-6-substituted-2-pyridones                                Compound   A      B        C    D     E    F                                  ______________________________________                                        Example 1  256    ≧1024                                                                           128  512   512  512                                Example 2  64     64       8    32    8    16                                 Example 3  32     32       2    2     16    2                                 Example 4  32     16       4    2     32    4                                 Example 5  256    16       8    32    8    nt                                 Example 6  512    64       128  256   256  nt                                 Example 7  64     128      16   64    64   nt                                 Example 8  256    8        1024 1024  1024 nt                                 Example 9  256    512      32   256   512  nt                                 Example 10 32     32       8    16    32   16                                 Example 11 16     16       4    4     8    16                                 Example 12 256    64       8    16    64   64                                 OCTOPIROX ®                                                                          128    64       2    2     2    16-32                              biocide                                                                       ______________________________________                                         A = Escherichia coli                                                          B = Staphylococcus aureus                                                     C = Candida albicans                                                          D = Fusarium sp.                                                              E = Aspergillus niger                                                         F = Aureobasidium pullulans                                                   "nt" denotes not tested                                                  

The results provided in Table 1 show that the compounds of the presentinvention provide MIC's that are sometimes better than those provided bya commercial biocide, OCTOPIROX® biocide, a product of Hoechst Company.Note that the compounds of Examples 3, 4 and 11 provide particularlyexcellent MIC results.

What is claimed is:
 1. A compound of the formula: ##STR4## wherein Y isa sulfur, or NR' moiety, wherein N is nitrogen and R and R' areindependently each a substituted or unsubstituted hydrocarbon radicalhaving from 1 to 20 carbon atoms.
 2. The compound of claim 1 wherein Ror R' is an aliphatic or aromatic hydrocarbon having from 2 to 18 carbonatoms, with the proviso that said aromatic hydrocarbon have at least 6carbon atoms.
 3. The compound of claim 1 wherein R or R' is a straightchain hydrocarbon having from 5 to 10 carbons.
 4. The compound of claim1 wherein R or R' is an n-octyl moiety.
 5. A compound of the formula:##STR5## wherein R" and R'" are independently either hydrogen or asubstituted or unsubstituted hydrocarbon radical having between 1 and 20carbon atoms.
 6. The compound of claim 5 wherein R" or R'" is analiphatic or aromatic hydrocarbon having from 2 to 18 carbon atoms, withthe proviso that said aromatic hydrocarbon have at least 6 carbon atoms.7. The compound of claim 5 wherein R" or R'" is a straight chainhydrocarbon having from 5 to 10 carbons.
 8. A compound of the formula:##STR6## wherein R" and R'" are independently either hydrogen or asubstituted or unsubstituted hydrocarbon radical having between 1 and 20carbon atoms, andwherein R" or R'" is an n-octyl moiety.
 9. A processfor producing the compound of claim 1, wherein Y in the formula of claim1 is oxygen, which comprises the steps of:(a) reacting2,6-dichloropyridine N-oxide, a hydroxy compound containing from 1 to 20carbon atoms and a base, optionally in the presence of water or anorganic solvent, to produce a corresponding2-chloro-6-substituted-pyridine N-oxide, and (b) reacting said2-chloro-6-substituted-pyridine N-oxide with a sulfur-containing base toproduce the corresponding1-hydroxy-6-substituted-pyridine-2-thione,steps (a) and (b) beingcarried out at a temperature independently selected from about 25 toabout 150 degrees Centigrade.
 10. A process for producing a compound ofclaim 1, wherein Y in the formula of claim 1 is NR' which comprises thesteps of:(a) reacting 2,6-dichloropyridine N-oxide, a primary orsecondary amine containing from 1 to 20 carbon atoms and a base,optionally in the presence of water or an organic solvent, at anelevated temperature to produce a corresponding2-chloro-6-substituted-pyridine N-oxide, and (b) reacting said2-chloro-6-substituted-pyridine N-oxide with a sulfide or hydrosulfidesalt to produce the corresponding1-hydroxy-6-substituted-pyridine-2-thione,steps (a) and (b) beingcarried out at a temperature independently selected from about 25 toabout 150 degrees Centigrade.
 11. A process for producing a compound ofclaim 1, wherein Y in the formula of claim 1 is sulfur, which comprisesthe steps of:(a) reacting a 2,6-dichloropyridine N-oxide, a thiolcompound having from 1 to 20 carbon atoms, and base in an organicsolvent at an elevated temperature to produce a corresponding2-chloro-6-substituted-pyridine N-oxide, and (b) reacting said2-chloro-6-substituted-pyridine N-oxide with a sulfide or hydrosulfidesalt to produce the corresponding1-hydroxy-6-substituted-2-pyridine-2-thione,steps (a) and (b) beingcarried out at a temperature independently selected from about 25 toabout 150 degrees Centigrade.
 12. A process for producing a compound ofclaim 5 which comprises the steps of:(a) reacting 2,6-dichloropyridineN-oxide, a primary or secondary amine containing from 1 to 20 carbonatoms and a base, optionally in the presence of water or an organicsolvent, at an elevated temperature to produce a corresponding2-chloro-6-substituted-pyridine N-oxide, and (b) reacting said2-chloro-6-substituted-pyridine N-oxide with a base to produce thecorresponding 1-hydroxy-6-substituted-pyridine-2-one,steps (a) and (b)being carried out at a temperature independently selected from about 25to about 150 degrees Centigrade.
 13. An antimicrobial compositioncomprising a functional product selected from the group consisting ofshampoos or skin care medicaments further comprising an antimicrobiallyeffective amount of a compound of the formula: ##STR7## wherein Y is anoxygen, sulfur, or NR' moiety, wherein N is nitrogen and R and R' areeach a substituted or unsubstituted hydrocarbon radical having between 1and 20 carbon atoms and conventional antimicrobial additives.
 14. Thecomposition of claim 13 wherein R or R' in said formula is an aliphaticor aromatic hydrocarbon having from 3 to 18 carbons.
 15. The compositionof claim 13 wherein R or R' in said formula is a straight chainhydrocarbon having from 5 to 10 carbons.
 16. The compound of claim 1wherein R or R' in said formula is an n-octyl moiety.
 17. A method forinhibiting the growth of microorganisms by contacting saidmicroorganisms on skin or scalp with a shampoo or skin care compositioncomprising an antimicrobial effective amount of a compound of theformula: ##STR8## wherein Y is an oxygen, sulfur, or NR' moiety, whereinN is nitrogen and R and R' are each a substituted or unsubstitutedhydrocarbon radical having between 1 and 20 carbon atoms.
 18. Anantimicrobial composition comprising a functional product selected fromthe group consisting of shampoos or skin care medicaments, furthercomprising an antimicrobially effective amount of a compound of theformula: ##STR9## wherein R" and R'" are independently either hydrogenor a substituted or unsubstituted hydrocarbon radical having between 1and 20 carbon atoms and conventional antimicrobial additives.
 19. Thecomposition of claim 18 wherein R" or R'" in said formula is analiphatic or aromatic hydrocarbon having from 3 to 18 carbons.
 20. Thecomposition of claim 18 wherein R" or R'" in said formula is a straightchain hydrocarbon having from 5 to 10 carbons.
 21. The composition ofclaim 18 wherein R" or R'" in said formula is an n-octyl moiety.
 22. Amethod for inhibiting the growth of microorganisms by contacting saidmicroorganisms or skin or scalp with a shampoo or skin care compositioncomprising an antimicrobial effective amount of a compound of theformula: ##STR10## wherein R" and R'" are either hydrogen or asubstituted or unsubstituted hydrocarbon radical having between 1 and 20carbon atoms and conventional antimicrobial additives.
 23. Anantimicrobial composition comprising a functional product selected fromthe group consisting of shampoos or skin care medicaments and furthercomprising an antimicrobially effective amount of a compound of theformula: ##STR11## wherein X is an oxygen or sulfur moiety and R is asubstituted or unsubstituted hydrocarbon radical having between 1 and 20carbon atoms, with the proviso that R is other than chlorobenzyl.